The primary goals of this research are i) to establish differences in brain processing in the context of nervous system damage or dysfunction, and ii) to determine the potential for learning-induced plasticity to ameliorate the negative consequences of such changes. Over the past year we have primarily focused on Autism Spectrum Disorders (ASD) and the impact of amputation, and on establishing the structural brain changes that accompany learning/training. 1) Loss of somatosensory input (Protocol 08-M-0052, NCT00623818) Following limb amputation, over 90% of people report phantom sensations in their missing limb, often painful sensations (Phantom Limb Pain, or PLP). One current theory suggests that PLP is a direct result of cortical reorganization, an example of maladaptive plasticity. Mirror therapy has been used as a treatment for PLP. During this therapy, patients move their intact limb while looking in a mirror, making it seem as if their missing limb is moving. We are currently investigating the neural consequences of amputation and the impact of mirror therapy on brain activity over time. We are continuing to recruit unilateral limb amputees and monitoring brain activity with fMRI over a period of four weeks while the amputees undergo mirror therapy. We are trying to establish whether the presence of PLP correlates with cortical reorganization in the somatosensory and motor cortex (similar to that observed in our participants with macular degeneration) and whether the mirror therapy works by reducing the extent of cortical reorganization. 2) Autism Spectrum Disorders (Protocol 10-M-0027, NCT01031407) We have been investigating motion processing, decision-making and attention in Autism Spectrum Disorders (ASD), processes that are supported by well-characteristic brain networks. Previously, we reported evidence for impaired motion processing in ASD. By varying the time allowed to make judgments, we found that motion processing in ASD was weaker then in matched control participants, but only at short durations. We followed up these results with a brain imaging study using fMRI, and found that responses to motion stimuli were reduced in ASD participants even in the earliest stages of cortical visual processing (primary visual cortex, V1). Further, consistent with the behavioral data, this effect was observed only at short stimulus durations (Robertson et al, 2014, Brain). We also investigated potential imbalance between excitation and inhibition in cortex, which has been a central component of many models of autistic neurobiology. Binocular rivalry, the tendency for visual stimuli presented separately to the two eyes to compete with each other and produce an alternating percept, is thought to reflect the push and pull of excitatory and inhibitory cortical dynamics. We found a slower rate of binocular rivalry alternations in ASD, and the rate was predictive of clinical measures of autistic symptomatology, supporting the notion that atypical cortical dynamics may underlie some of the symptoms of autism (Robertson et al, 2013, Journal of Neuroscience). 3) Learning/training (Protocol 93-M-0170, NCT00001360) We are conducting a long-term longitudinal study of participants learning different tasks (e.g. motor sequences) to determine how structural properties of the brain change over time. Over a period of four weeks, participants are trained in two different tasks and we collect extensive functional and structural MRI data over the course of training. Establishing the nature, degree and consequences of plasticity in the adult cortex provides important insights into the potential for rehabilitative brain therapies following injury or dysfunction in the nervous system.